Cytomegalovirus infection induces T‐cell differentiation without impairing antigen‐specific responses in Gambian infants

Miles, David J. C.; Sanneh, Mariama; Holder, Beth; Crozier, Sarah; Nyamweya, Samuel; Touray, Ebrima; Palmero, Melba S.; Zaman, Syed M A; Rowland‐Jones, Sarah; Sande, Marianne A. B. van der; Whittle, Hilton

doi:10.1111/j.1365-2567.2007.02787.x

Cited by 50 publications

(64 citation statements)

References 61 publications

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“…The greater importance of central memory subpopulation size at the time of re-exposure than at first exposure is supported by evidence from a previous study on proliferative responses to the measles vaccine 21. There, central memory subpopulation size differed between treatments at the time of vaccination but not by the time of re-exposure, and proliferative responses following re-exposure were also similar between the treatment groups.…”

Section: Discussionmentioning

confidence: 57%

Human immunodeficiency virus (HIV) infection during pregnancy induces CD4 T‐cell differentiation and modulates responses to Bacille Calmette‐Guérin (BCG) vaccine in HIV‐uninfected infants

et al. 2010

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Human immunodeficiency virus (HIV)-negative infants born to HIV-positive mothers frequently exhibit a range of immunological abnormalities. We tested the hypothesis that HIV during pregnancy affects the ability of CD4 T cells of HIV-negative infants to respond to vaccine challenge by recruiting HIV-negative infants born to HIV-negative and HIV-positive mothers and measuring their responses to Bacille Calmette-Guérin (BCG) vaccine given at birth. At 2 weeks, maternal HIV status did not influence CD4 T-cell counts or differentiation, but by 10 weeks CD4 counts of infants born to HIV-positive mothers fell to a level characteristic of HIV-positive infants. Among the CD4 T-cell populations, markers of differentiation (CCR7− CD45RA− CD27−) and senescence (CD57, PD-1) were more common among infants born to HIV-positive mothers than among infants born to HIV-negative mothers. At 2 weeks of age, we assessed the effector response to heat-killed BCG and tuberculin purified protein derivative (PPD) by overnight interferon (IFN)-γ enzyme-linked immunosorbent spot-forming cell assay (ELISpot), but found no measurable effect of maternal HIV status. At 10 weeks, we assessed CD4 T-cell memory by measuring proliferation in response to the same antigens. We observed a bimodal response that allowed infants to be classified as high or low responders and found that fewer infants born to HIV-positive mothers were able to mount a robust proliferative response, suggesting that their reduced CD4 counts and increased differentiation indicated a deficiency in their ability to develop immunological memory.

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Section: Discussionmentioning

confidence: 57%

Human immunodeficiency virus (HIV) infection during pregnancy induces CD4 T‐cell differentiation and modulates responses to Bacille Calmette‐Guérin (BCG) vaccine in HIV‐uninfected infants

et al. 2010

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“…Given the results of this study, it seems unlikely that primary immune responses which involve the naive T cell compartment or CD4 + T cell-dependent immune responses in ESRD patients will be affected by their CMV serostatus. At present, such an association has not been reported and CMV serostatus does not seem to affect the vaccination response in children [32,33].…”

Section: Cd28mentioning

confidence: 75%

Cytomegalovirus contributes partly to uraemia-associated premature immunological ageing of the T cell compartment

Meijers

Litjens

Wit

et al. 2013

Clinical and Experimental Immunology

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SummaryCytomegalovirus (CMV) infection has been implicated in accelerated T cell ageing. End-stage renal disease (ESRD) patients have a severely immunologically aged T cell compartment but also a high prevalence of CMV infection. We investigated whether CMV infection contributes to T cell ageing in ESRD patients. We determined the thymic output by the T cell receptor excision circle (TREC) content and percentage of CD31+ naïve T cells. The proliferative history of the T cell compartment by determination of the relative telomere length (RTL) and the T cell differentiation status was determined by immunophenotyping. It appeared that CMV infection did not affect thymic output but reduced RTL of CD8+ T cells in ESRD patients. Moreover, increased T cell differentiation was observed with higher percentages of CD57+ and CD28null CD4+ and CD8+ memory T cells. These CD28null T cells had significantly shorter telomeres compared to CD28+ T cells. Therefore we concluded that CMV infection does not affect the decreased thymic output but increases T cell differentiation as observed in ESRD-related premature T cell ageing.

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“…The immune response that eventually controls oral CMV shedding is likely multifactorial [20][21][22][23][24]. For simplicity, we constructed a model that assumed clearance of oral shedding results from a mounting cytolytic response based on a saturated process [25].…”

Section: Mathematical Modeling Of the Oral Immune Response To CMVmentioning

confidence: 99%

Dynamics of Persistent Oral Cytomegalovirus Shedding During Primary Infection in Ugandan Infants

Mayer¹,

Matrajt²,

Casper³

et al. 2016

J Infect Dis.

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Cytomegalovirus (CMV) infection occurs frequently in young children, who, when infected, are then a major source of transmission. Oral CMV shedding by 14 infants with primary infection was comprehensively characterized using quantitative polymerase chain reaction weekly for ≥9 months. Three phases of oral shedding were identified: expansion, transition, and clearance. Viral expansion occurred over a median of 7 weeks, with a median doubling time of 3 days. During the transition phase, expansion slowed over a median of 6 weeks before peak viral load was reached. Clearance was slow (22-day median half-life), and shedding did not resolve during observation for any infant. Mathematical modeling demonstrated that prolonged oral CMV expansion is explained by a low within-host reproduction number (median, 1.63) and a delayed immune response that only decreases the infected cell half-life by 44%. Thus, the prolonged oral CMV shedding observed during primary infection can be explained by slow viral expansion and inefficient immunologic control.Keywords. epidemiology; cytomegalovirus; transmission; mathematical model; immunology; theoretical biology.Worldwide, most primary cytomegalovirus (CMV) infections occur during early childhood, through the oral route [1]. Infected infants shed CMV orally at high, persistent levels [2-6] and are a major source of transmission, including to pregnant women, which contributes to congenital infection [3,[7][8][9]. Viral dynamics during primary infection are governed by properties of viral infectivity and the immune response. A detailed study of these processes could identify immunologic thresholds necessary for effective vaccination. Here, we use mathematical models to describe oral shedding dynamics during primary CMV infection in a cohort of Ugandan infants. MATERIALS AND METHODS Study Cohort and DataAs previously described [10], pregnant women in Kampala were enrolled, and oral swabs were collected in a standardized manner [11] from the mother and all children for quantitative polymerase chain reaction (qPCR) analysis of CMV [12]. Blood samples were collected from the infants at 6 weeks of age and every 4 months thereafter. Oral swabs and plasma samples were tested for CMV, using real-time qPCR. Primary infection was defined virologically and serologically as described elsewhere [10]. Additional information about subject selection is provided in the Supplementary Materials. This study was approved by all relevant institutional review boards in Uganda, the United States, and Canada. Written informed consent was obtained from all study participants or their guardians. Statistical Analysis and Classification of EpisodesEpisode duration was defined as the interval from the start of oral shedding until the end of observation. Correlations between same-day log 10 copies of CMV in plasma and oral swabs were calculated using Pearson correlation for all values and for positive values only. To see whether positive plasma samples were associated with higher oral log 10 CMV levels, we performed ...

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Cytomegalovirus infection induces T‐cell differentiation without impairing antigen‐specific responses in Gambian infants

Cited by 50 publications

References 61 publications

Human immunodeficiency virus (HIV) infection during pregnancy induces CD4 T‐cell differentiation and modulates responses to Bacille Calmette‐Guérin (BCG) vaccine in HIV‐uninfected infants

Human immunodeficiency virus (HIV) infection during pregnancy induces CD4 T‐cell differentiation and modulates responses to Bacille Calmette‐Guérin (BCG) vaccine in HIV‐uninfected infants

Cytomegalovirus contributes partly to uraemia-associated premature immunological ageing of the T cell compartment

Dynamics of Persistent Oral Cytomegalovirus Shedding During Primary Infection in Ugandan Infants

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